Implants are utilized in modern medical technology in a variety of embodiments. They are used e.g. to support vessels, hollow organs, and ductal systems (endovascular implants e.g. stents), to attach and temporarily fix tissue implants and tissue transplants in position, and for orthopedic purposes such as pins, plates, or screws. The stent is a form of an implant that is used particularly frequently.
Stent implantation has become established as one of the most effective therapeutic measures for treating vascular disease. Stents are used to provide support in a patient's hollow organs. For this purpose, stents of a conventional design have a filigree support structure composed of metallic struts; the support structure is initially provided in a compressed form for insertion into the body, and is expanded at the application site. One of the main applications of stents of this type is to permanently or temporarily widen and hold open vasoconstrictions, in particular constrictions (stenoses) of the coronary arteries. In addition, aneurysm stents are known, for example, which are used primarily to seal the aneuryism. They also perform the support function.
Stents include a circumferential wall having a support force that suffices to hold the constricted vessel open to the desired extent; stents also include a tubular base body through which blood continues to flow without restriction. The circumferential wall is typically formed by a latticed support structure that enables the stent to be inserted, in a compressed state having a small outer diameter, until it reaches the constriction in the particular vessel to be treated, and to be expanded there, e.g. using a balloon catheter, until the vessel finally has the desired, enlarged inner diameter. Alternatively, materials having a memory effect, such as Nitinol, are capable of self-expansion in the absence of a restoring force that holds the implant at a small diameter. The restoring force is typically exerted on the material by a protective tube.
The implant, in particular the stent, has a base body composed of an implant material. An implant material is a nonliving material that is used for a medical application and interacts with biological systems. A prerequisite for the use of a material as an implant material that is comes in contact with the physical surroundings when used as intended is its biocompatibility. “Biocompatibility” refers to the capability of a material to evoke an appropriate tissue response in a specific application. This includes an adaptation of the chemical, physical, biological, and morphological surface properties of an implant to the recipient tissue, with the objective of achieving a clinically desired interaction. The biocompatibility of the implant material is furthermore dependent on the time sequence of the response of the biosystem in which the implant is placed. For example, irritations and inflammations, which can cause tissue changes, occur over the relative short term. Biological systems therefore respond differently depending on the properties of the implant material. Depending on the response of the biosystem, implant materials can be subdivided into bioactive, bioinert, and degradable/resorbable (referred to here as biocorrodible) materials.
Implant materials include polymers, metallic materials, and ceramic materials (as a coating, for example). Biocompatible metals and metal alloys for permanent implants contain e.g. stainless steels (e.g. 316L), cobalt-based alloys (e.g. CoCrMo casting alloys, CoCrMo forging alloys, CoCrWNi forging alloys, and CoCrNiMo forging alloys), pure titanium and titanium alloys (e.g. CP titanium, TiAl6V4 or TiAl6Nb7), nickel-titanium alloys (e.g. NiTiNo1), and gold alloys. In the field of biocorrodible stents, the use of magnesium or pure iron and biocorrodible base alloys of the elements magnesium, iron, zinc, molybdenum, and tungsten is proposed.
It is known that a greater level of biocompatibility can be achieved by coating implant materials with particularly tissue-compatible materials. These materials are usually organic or synthetic-polymeric in nature and are partially of natural origin. Further strategies for preventing restenosis focus on inhibiting proliferation using medication e.g. treatment using cytostatic agents. The active agents can be provided e.g. on the implant surface in the form of a coating that releases an active agent.
The active agents are applied directly as a coating or are embedded in an elution matrix. In the case of implants composed of biocorrodible materials in particular, it should also be possible for the elution matrix to be degraded in vivo. The disadvantage of degradable and permanent polymers, which are typically used in active-agent-eluting implants as an elution matrix, is that they induce inflammatory responses at the implantation site over the long-term, thereby affecting the clinical result. A polymer-based elution matrix should therefore be eliminated if possible.
Implants without a polymer-based elution matrix are basically known from the prior art. The substance, which usually has an antiproliferative effect, can be applied in pure form or in a mixture with an excipient (auxiliary agent as the carrier) directly to the surface of the implant which can be smooth, roughened, or provided with structural recesses and which are used as a reservoir.
Such implants have the disadvantage, however, that adhesion to the vascular wall is delayed, or occurs only partially or not at all over the long term. The risk therefore results e.g. of stent thrombosis occurring over the long term; to prevent this, systematic anticoagulation therapy is applied in clinical practice. This “dual antiplatelet therapy” (DAPT) has numerous clinical disadvantages that ultimately must be put up with in the form of delayed (or the absence of) adhesion of conventional implants.